CTTI Advancing the Use of Central IRBs for Multicenter Clinical Trials
Template IRB Authorization Agreement
Background
CTTI has recommended[1] the use of a single IRB of record[2] for multi-center clinical trials. To facilitate adoption of this model, CTTI has developed tools and resources for sponsors, institutions, and organizations that serve as a central IRB. This template IRB Authorization Agreement (IAA) is intended to address an administrative concern about using a single central IRB for multicenter clinical trials.
How was the template IRB Authorization Agreement drafted?
This template IAA is the work product of the CTTI Advancing the Use of Central IRBs for Multicenter Clinical Trials project team and an additional 46 experts from the Human Research Protection Program community who came together during a 2-day expert meeting held June 12-13, 2014 in Rockville, MD.
Prior to the expert meeting, a request was made on the IRB Forum Listserv in July 2013 asking for members of the Institutional Review Board (IRB) community who allow reliance on or who serve as a central IRBs to share their template agreements with the CTTI project team. Twenty institutions and organizations agreed to be part of the initial data collection process where template IRB agreements were reviewed to determine domains, the kinds of clauses included in each domain, and the frequency that those clauses appeared. Once common domains and clauses were established, the CTTI Central IRB Advancement project team reviewed example clauses and created a working draft which was then further evaluated during an expert meeting and finally validated by attendees post meeting.
What kinds of IRBs submitted their template agreements for review?
Note: total is greater than 100% as IRBs may have been associated with more than one role.
· Institutional IRBs: 56%
· Commercial/Independent IRBs: 31%
· IRBs associated with a federal sponsor: 30%
· IRBs associated with a clinical trial network: 30%
This template IAA may be used as a tool to help organizations move forward with centralized IRB review where appropriate. It represents the consensus of meeting attendees and should not be construed as the opinion of any one individual attendee nor does it represent an explicit endorsement by the federal agencies in attendance.
Name of Organization Providing IRB Review (hereinafter, “Central IRB”):
IRB Registration NumberStreet Address
City
State (if US)
Zip/Postal Code
Country
Name of Individual Responsible for
Administration of the IAA
Title of Individual
Phone Number
Email address
Name of Institution Relying on the Reviewing IRB (hereinafter, “Institution”):
Institution’s OHRP Federalwide Assurance(FWA) #, if applicable
Name of Institutional Official
Street Address
City
State (if US)
Zip/Postal Code
Country
Name of Individual Responsible for
Administration of the IAA
Title of Individual
Phone Number
Email address
1. Scope of the Agreement:
1.1 The Officials signing below agree that Institution shall rely on Central IRB for review and continuing oversight of human subject research covered by the Institution’s FWA, if applicable.
OR, if project specific
The Officials signing below agree that Institution shall rely on Central IRB for review and continuing oversight of the following human subject research covered by the Institution’s FWA:
Title of Research ProjectName of Principal Investigator
Name of Sponsor
Name of Funding Agency
Award Number, if any
1.2 This Agreement does not preclude any party from participating in any other IRB authorization agreements that it may have or enter with other entities for human subject research other than the study for which review is ceded to the Central IRB under this Agreement. This document must be kept on file by all parties and provided to FDA, OHRP, and/or other applicable regulatory agencies upon request. This Agreement may be executed in any number of counterparts, either in original, emailed or faxed form.
1.3 The Central IRB will follow Institution/Central IRB (pick one)’s policies and procedures pertaining to documentation and review. For the purposes of conducting the IRB review, Institution/ Central IRB (pick one) will identify and interpret the requirements of applicable state or local laws, and regulations. Institution shall have the ability to discuss these interpretations with the Central IRB
2. Responsibilities of the Central IRB
2.1 The review performed by Central IRB will meet the human subject protection requirements of the Common Rule (e.g., 45 CFR 46) and applicable FDA regulations (e.g., 21 CFR Parts 50, 56, 312, 812). Central IRB will follow written procedures for reporting its findings and actions to the PI, Sponsor, and appropriate officials at the Institution and federal agencies as appropriate. Relevant minutes of IRB meetings may be made available to the Institution by Central IRB upon request.
2.2 Central IRB services shall include, but not be limited to:
§ review and approval or disapproval of new protocols;
§ review and approval, disapproval or modification of consent forms or waivers of informed consent;
§ review and approval of modifications to protocols;
§ review and approval or disapproval of the investigator(s) and changes in research;
§ collection of reports of unanticipated problems and serious or continuing noncompliance;
§ maintenance of required IRB records pursuant to applicable federal regulations.
§ continuing review of certain new research studies appropriate to the degree of risk in such studies. Central IRB agrees to conduct at least an annual review of each non exempt study.
2.3 Central IRB shall promptly notify the Principal Investigator (PI) of the study as designated on the IRB protocol submission of all IRB decisions and shall make available to the PI all applicable study related documents including but not limited to approved protocols, consent forms, surveys, and decision letters.
2.4 Central IRB shall notify the institution promptly
§ if there is ever a suspension or restriction of the IRB’s authorization to review studies;
§ of any changes in Central IRB operating procedures or practices that might affect the institution’s reliance on Central IRB reviews;
§ of complaints from human subjects enrolled in studies at the institution;
§ of unanticipated problems involving injury or risks to subjects or others in the study;
§ if the Central IRB determines that serious or continuing non-compliance has occurred, and any steps the Central IRB deems necessary for remediation of non-compliance;
§ of suspension or termination of IRB approval;
§ of any communication with the FDA, OHRP or funding agency of matters relevant to human subject protections and relating to the institution’s studies; or
§ changes in accreditation status, if applicable.
2.5 HIPAA If applicable (optional) Central IRB will perform those determinations required by the Health Insurance Portability and Accountability Act of 1996 and its implementing regulations (collectively, “HIPAA”) with respect to the use and disclosure of Protected Health Information (“PHI”) for the research protocol in this Agreement, including authorization and waivers of authorization for use and disclosure of PHI. If it becomes necessary for the parties to use or disclose PHI in any way not covered by the existing authorization or waiver of authorization, then the parties will work together to determine any additional steps necessary to ensure that the required information is used or disclosed in a HIPAA-compliant manner
3. Responsibilities of the Institution
3.1 The Institution shall ensure investigator compliance with the protocol, IRB determinations, applicable federal and state regulations, sponsor requirements, and if applicable with the terms of its OHRP-approved FWA.
3.2 The institution shall ensure prompt reporting to the IRB of proposed changes in a research activity, and ensure that such changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to the subject.
3.3 Institution shall provide all information reasonably required by Central IRB in order to conduct its reviews and will facilitate Central IRB access to Institution expertise when needed. Institution cannot approve any research study that has been disapproved by the Central IRB. Institution may, however, disapprove any study approved by the Central IRB. Institution agrees to abide by the decisions of the Central IRB and shall use its best efforts to ensure that the human subject research performed by Institution shall be conducted in accordance with those decisions.
3.4 Institution shall ensure that investigators and other study personnel at the institution are qualified and have appropriate resources to conduct the research, including but not limited to education and training in human research protection regulations. The institution shall provide documentation of training and education, as requested by the Central IRB.
3.5 Institution shall ensure an institutional process exists by which complaints about the study can be made by local study participants or others. Complaints that meet criteria as a potential unanticipated problem involving risks to subjects or others or serious or continuing noncompliance must be reported to the Central IRB in accordance with the timeframe specified by the Central IRB.
3.6 Institution shall cooperate with any Central IRB investigation regarding serious or continuing noncompliance or an unanticipated problem involving risk to subjects or others related to the study at the institution. Nothing in this Agreement shall prevent either party from conducting its own investigation. However, Central IRB shall have primary authority to determine whether serious or continuing noncompliance or unanticipated problems involving risks to subjects or others have occurred.
3.7 Institution shall notify the Central IRB promptly:
§ if there is ever a suspension or restriction of the Institution’s authorization or ability to conduct studies;
§ of any changes in institutional operating procedures or practices that might affect the Central IRB’s ability to review for the institution;
§ of complaints from human subjects enrolled in studies reviewed by the Central IRB which involve potential unanticipated problems involving risks to subjects or others;
§ of unanticipated problems involving injury or risks to subjects or others in a study reviewed by the Central IRB;
§ if the Institution believes that serious or continuing non-compliance has occurred in a study reviewed by the Central IRB, and any steps the Institution deems necessary for remediation of non-compliance;
§ of suspension or termination of Institutional approval;
§ of any communication with the FDA, OHRP or funding agency relating to the institution’s studies being reviewed by the Central IRB;
§ changes in accreditation status, if applicable.
3.8 Federally Funded Studies (optional, if applicable): Institution will maintain a current, approved Federalwide Assurance (FWA) with OHRP for the duration of this Agreement. The Institution will notify the Central IRB promptly in writing if its FWA is suspended or expires for any reason.
4. Joint Responsibilities
4.1 Confidentiality Each party is authorized to exchange information pursuant to this Agreement and agrees to treat such information as confidential (Confidential Information). No Party shall disclose Confidential Information received pursuant to this Agreement to any individual or entity other than another Party without prior written approval of all Parties. Notwithstanding the foregoing, nothing in this Agreement shall be construed to restrict a Party from disclosing Confidential Information as required by law, subpoena, court order, or other governmental order or request. Institution shall cause Principal Investigator and all other research personnel to comply with the terms and conditions of this section in the same manner as such terms and conditions apply to Institution. This section shall survive the termination of this Agreement.
4.2 Protected Health Information (Optional, if applicable) The parties shall hold in confidence the identity of the participants in any Studies and shall comply with applicable laws regarding confidentiality of individually-identifiable subject information and the requirements of any authorization executed by subjects for a given study. . Each party shall comply with all applicable laws and regulations, including, but not limited to, HIPAA, relating to the use and disclosure and privacy and security of individually identifiable health information of human subjects (“Subject Health Information”). Each party shall use and disclose Subject Health Information only as authorized by the subject or legally-authorized representative pursuant to subjects’ written authorization and informed consent forms. Each party shall notify the other party orally and in writing within twenty-four (24) hours of its discovery of any Subject Health Information in its possession, which is improperly used or disclosed in violation of HIPAA or the applicable subject authorization, and serious or continuing noncompliance. The parties shall cooperate with each other in taking such steps as are deemed appropriate, to enjoin misuse, regain possession of the data, and otherwise protect each parties’ rights and subjects’ privacy. It is expressly understood that, by providing review services as described herein, Central IRB shall not be regarded as a “Business Associate” of Institution
4.3 Record Keeping Central IRB and Institution agree to maintain records in compliance with all applicable federal, state, and local regulations regarding record retention and agree to make to records available when and as required by law.
4.4 Federal Regulatory Agency Review Central IRB and Institution agree to notify the other party when a federal regulatory agency has or will conduct an audit or review of a study applicable to this authorization agreement and will notify each party of the outcome of the review.
4.5 Inspection Central IRB or its authorized representatives shall be permitted upon request to: (1) examine and inspect Institution’s facilities used for the performance of its research, including storage and use of any investigational products; (2) observe the conduct of the research performed at the Institution; (3) inspect and copy all documents relating to its studies, including study records and informed consent documents, investigational product logs, required licenses, certificates and accreditations; and (4) interview all necessary personnel involved in the research conduct of its studies.
Likewise the Institution shall be permitted upon request to (1) obtain copies of all applicable IRB correspondence pertaining to activities hereunder; (2) review Central IRB’s policies, procedures, roster and other information pertinent to board functions; and (3) inspect and copy all documents relating to its studies, including but not limited to protocols and informed consent documents, investigational drug brochures, reports, unanticipated problems, reports of noncompliance, required licenses, certificates and accreditations.